P1659: STUDY AND POSSIBLE DIAGNOSIS OF PATIENTS WITH THROMBOTIC MICROANGIOPATHIES WHO PRESENT ADAMTS13 ACTIVITIES BETWEEN 5-10%
Authors: Marta Molina-Pérez, Jorge M. Nieto, Paloma Ropero Gradilla, Silvia Escribano Serrat, Miguel Gómez Álvarez, Horacio Gulino, Pablo Estival Monteliú, Antonio Chamorro Fernández, María Eva Mingot, José García Gala, María Cristina Vega Cabrera, Irene Amores Hernández, Juan Churruca Sarasqueta, Mónica Bonete Román, Ataulfo González Fernández, Ana Villegas, Celina Benavente Cuesta
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Thrombotic Thrombocytopenic Purpura (TTP) is a hematological emergency characterized by a severe deficiency of ADAMTS13. Depending on the consulted publication, ADAMTS13 deficiency is defined as an activity <5% or <10%. This generates uncertainty in the diagnosis when patients exhibit ADAMTS13 activity levels within the range of 5-10%. Aims: The aims are to determine, in a large Thrombotic Microangiopathy (TMA) cohort, the proportion of patients who exhibit ambiguous ADAMTS13 activities, and to explore potential reasons for the observed reduced levels of ADAMTS13 in these patients. Methods: Our hospital has received 2999 samples from 2017 patients with TMA for the determination of ADAMTS13 (ELISA, Technoclone). Cases with activities between 5-10% at diagnosis were selected, and the following variables were studied: TTP score, associated clinical conditions, ADAMTS13 activity at onset and in complete response (CR), treatment and response, ADAMTS13 inhibitor, anti-ADAMTS13 IgG and ADAMTS13 genetics. Results: Most diagnostic determinations (n=1958; excluding follow-ups and TTP relapses) result in activities less than 5% (13.7% of the determinations) or greater than 10% (85.9% of the determinations). Only 8 patients with activities between 5-10% were identified (0.4% of the total). Three of them (#1-3) have a final diagnosis of acquired TTP due to the presence of inhibitors or anti-ADAMTS13 IgG antibodies. One patient was found to have a homozygous pathogenic mutation in the ADAMTS13 gene, being diagnosed with congenital TTP (#4) (Table 1). In the remaining 4 cases, a clear diagnosis of TTP could not be established. Two of these cases (#5 and #6) were patients with TMA associated with sepsis, who did not meet TTP scores and did not have autoimmunity against ADAMTS13 or genetic mutations. The last cases (#7 and #8), with a mild TMA, without inhibitors or IgG, only presented a heterozygous mutation in ADAMTS13. Summary/Conclusion: The number of determinations by ELISA with activities in the 5-10% range at diagnosis is very low. However, a result in this range can be problematic, as it cannot be concluded that all these patients have TTP. Sepsis is a well-established cause of TMA, which is generally associated with reduced levels of ADAMTS13 (48.8% in sepsis vs. 62.7% in other TMAs; p<0.001; U Mann-Whitney) in our cohort and others. An activity of 5-10% in a patient with sepsis should not be unequivocally considered as TTP, unless there are indications of autoimmunity against ADAMTS13. The role of heterozygous mutations in ADAMTS13 is unclear and is a field to be studied in the future. The partial recovery of activity levels in CR indicates that these two patients (#7 and #8) do not have additional mutations in ADAMTS13 that we have not detected. It is possible that in the presence of a strong trigger (such as postpartum, vasculitis, etc.), some heterozygous cases may exhibit temporarily reduced activity levels below 10%. Seven out of the eight patients recovered from the TMA condition, with some of them not even receiving plasma therapy (#1 and #7), suggesting that the severity of TMA may be lower in some cases with residual activity. In the patient who died, activity levels were falsely increased due to prior blood transfusions and plasma infusions, likely masking a more severe ADAMTS13 deficiency (<5%) in a patient with a very complex clinical presentation (#3).Keywords: ADAMTS13, Thrombotic thrombocytopenic purpura (TTP), Thrombotic microangiopathy